The present invention relates to new 4,5,6,7-tetrahydro-[1,2]dithiolo[4,3-c]pyridine-3-thione compounds, pharmaceutically acceptable salts thereof, or solvates or hydrates thereof. Specifically, the above 4,5,6,7-tetrahydro-[1,2]dithiolo[4,3-c]pyridine-3-thione compounds of the present invention directly activates p90 ribosomal S6 kinase 1 (RSK1) to increase its kinase activity, thereby resulting in phosphorylation of a specific residue of CCAAT-enhancer binding protein β (C/EBPβ) to form an activated form of C/EBPβ. The activated form of C/EBPβ regulates gene expression, thereby accelerating regeneration of liver cell. Also, the activated form of C/EBPβ inhibits expression of transforming growth factor β (TGFβ) which is a key factor of hepatic fibrosis, to prevent and treat hepatic fiborsis and cirrhosis.
Liver plays a pivotal role in metabolizing external and internal materials, and is a vital organ wherein enzyme reaction and energy metabolism continuously take place. At present, among chronic diseases in Korea, hepatitis, cirrhosis, and liver cancer are most frequent ones, along with circulatory organ diseases, and also take a big part among the causes of death due to diseases. Particularly, the population in drinking is relatively high, compared with advanced countries, and the possibility of liver damage due to heavy drinking is also high, and thus concern on the liver is high. Continuous liver tissue damage due to virus infection or drinking is a cause of chronic complex diseases which develop into cirrhosis or liver cancer. Considering physiological property and importance of liver tissue, treatment and prevention of liver diseases are very important. Thus, there has been a need to develop a technique searching and utilizing the treatment action point of a drug which can normalize liver function by reducing liver tissue damage and ultimately regenerating live cell.
The present inventors have already discovered that C/EBP's activity is an essential key transcription factor in cirrhosis treatment and live tissue regeneration through the preceding inventions [Korean Patent Application No. 2000-18134 and Korean Patent No. 0377789]. They have continuously searched a cell signal which mediates a change of expression of main genes related to hepatic fibrosis and cirrhosis. As a result, they surprisingly discovered that the compounds of formula (I) directly increase RSK1's kinase activity, and such directly increased RSK1's activity can treat hepatic fibrosis and cirrhosis. Therefore, the present inventors completed the present new compounds of formula (I) which can directly increase RSK1's kinase activity, and a pharmaceutically composition comprising them.